Aqueous ginseng extract has a preventive role in RANKL-induced osteoclast differentiation and estrogen deficiency-induced osteoporosis

• Ginseng showed anti-osteoporotic activity in vitro (osteoclast differentiation) and in vivo.
• This study also showed Rb1, Rg1, Rc, Re and Rf or its combined formulation inhibited osteoclast formation and RANKL-induced TRAP activity.
• Aqueous extracts are an especially popular formulation. Throughout this study, a simple hot water extraction of ginseng was applied.

Ginseng, a medicinal herb, has a large number of active ingredients including steroidal saponins, commonly known as ginsenosides, which have biological functions including anti-osteoporotic effects. In this study, six ginsenosides were identified in ginseng. Of these saponins, five ginsenosides (Rb1, Rg1, Rc, Re, and Rf) inhibited osteoclast formation, RANKL-induced tartrate-resistance acid phosphate (TRAP) activity, and formation of multinucleated osteoclasts in vitro. Consistently, an aqueous ginseng extract significantly inhibited osteoclast differentiation and also regulated expression of calcitonin receptor (Cal-R) and estrogen receptor-α (ER-α) mRNAs. In vivo, ginseng treatment was shown to have an anti-osteoporotic effect in ovariectomized (OVX) rats. Ginseng treatment delayed the increase in body weight associated with ovariectomy, affected bone structure and biochemical properties, and helped regulate bone mineral density and content. The ginseng-treated OVX group also showed decreased osteoclast number, inhibited osteoclast activity, and reversal of the reduced serum estradiol level. This study suggests that ginseng prevents postmenopausal bone loss by inhibiting osteoclast differentiation, a process controlled by estrogen.